Biogenic amine O- and N-methyltransferases will be purified from various human tissues and further characterized to determine their physiological role in the biosynthesis and inactivation of biogenic amine neurotransmitters and in the formation of psychotomimetic O- N-methyl derivatives of biogenic amines. The specific enzymes are catechol-O-methyltransferase (COMT), hydroxyindole-O-methyltransferase (HIOMT), nonspecific N-methyltransferase, serotonin- and tryptamine-N-methyltransferase, iodophenol-O-methyltransferase (IPOMT), 3,4,-dimethoxyphenenthylamine (DMPEA) forming and mescaline forming enzymes. Among these, catechol-O-methyltransferase (COMT) which has been shown to exhibit molecular heterogeneity in rats, will be examined for the possible existence of multiple molecular forms in human tissues, and further characterized to determine their physiological significance in the inactivation of catecholamine, with an emphasis on the possibility that the enzyme may be subject to allosteric control and on a possible link between the inactivation of catecholamine and steroid hormone. Catechol-di-O-methylating enzyme activities (DMPEA and mescaline forming enzymes), IPOMT, and indoleamine N-methyltransferases will be extensively characterized to assess their role in the formation of psychotomimetic O- and N-methyl derivatives of biogenic amines. Each individual enzyme will be subjected to extensive purification to determine molecular properties, substrate specificity, physiochemical, catalytic and kinetic properties. (Biogenic amine neurotransmitters, methylation, O- and N-methyltransferases, psychosis, molecular heterogeneity, isozymes of COMT, enzyme purification.)